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Structure, expression, and function of kynurenine aminotransferases in human and rodent brains

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Abstract

Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), an endogenous antagonist of N-methyl-d-aspartate and alpha 7-nicotinic acetylcholine receptors. Abnormal KYNA levels in human brains are implicated in the pathophysiology of schizophrenia, Alzheimer’s disease, and other neurological disorders. Four KATs have been reported in mammalian brains, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase. KAT II has a striking tertiary structure in N-terminal part and forms a new subgroup in fold type I aminotransferases, which has been classified as subgroup Iε. Knowledge regarding KATs is vast and complex; therefore, this review is focused on recent important progress of their gene characterization, physiological and biochemical function, and structural properties. The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed.

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Acknowledgment

This work was supported by a NS063836 grant, an Intramural Research Program of the institutes of NIDCR and NINDS at NIH. We are grateful to Elizabeth Watson (Department of Biochemistry, Virginia Tech) for critically reading this paper.

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Authors and Affiliations

  1. Department of Biochemistry, Virginia Tech, Blacksburg, VA, 24061, USA

    Qian Han & Jianyong Li

  2. OIIB, NIDCR, National Institutes of Health, Bethesda, MD, 20892-4322, USA

    Tao Cai

  3. Neuroscience Center, NINDS, National Institutes of Health, Bethesda, MD, 2089-29525, USA

    Danilo A. Tagle

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  1. Qian Han
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  2. Tao Cai
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  4. Jianyong Li
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Correspondence to Jianyong Li.

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Han, Q., Cai, T., Tagle, D.A. et al. Structure, expression, and function of kynurenine aminotransferases in human and rodent brains. Cell. Mol. Life Sci. 67, 353–368 (2010). https://doi.org/10.1007/s00018-009-0166-4

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  • DOI: https://doi.org/10.1007/s00018-009-0166-4

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